1. Field of the Invention
This invention relates to a method of reducing the pyrogenicity and infectivity of hepatitis B or other viruses in biological and pharmaceutical products. More particularly this invention relates to a method of inactivating viruses and pyrogens which contaminate biological and pharmaceutical products by adsorbing said products on a solid phase and subjecting them to a treatment with an agent which inactivates viruses and/or pyrogens.
2. Description of the Prior Art
It is well-known that biological and pharmaceutical products may contain transmissible biological contaminants, such as viruses, and especially infectious hepatitis viruses, such as hepatitis virus B, and non-A, non-B hepatitis viruses. Contamination by viruses may result from both the source material used and from the environment during their production.
Pyrogens are lipopolysaccharides also known as endotoxins, having numerous biologic activities which include the production of fever, activation of clotting mechanisms and induction of shock. Consequently, it is essential that pyrogenic substances be removed from products intended for biological or pharmaceutical use.
Methods for inactivation or destruction of viruses and/or pyrogens include treatment with heat, acid or alkali, filtration, removal by adsorption with gels, ion-exchange resin and various other such adsorbent material. Most of these methods are burdensome, time consuming, or destructive of the product due to the rigorousness of the treatment.
Simple treatment with virus or pyrogen inactivating agents like Triton, Tween, beta-propiolactone or hypochlorite may result in inactivation of the viruses and/or pyrogenic materials but is accompanied by partial denaturation of labile proteins. Even if the proteins are not denatured, the quantitative removal of the residual virus inactivating agent or pyrogen inactivating agent may be very difficult and its contamination makes the biological or pharmaceutical product undesirable.
Illustrative of the use of virus and/or pyrogen inactivating agents is U.S. Pat. No. 4,314,997 which discloses the use of amphiphiles to destroy endotoxin and to inactivate hepatitis viruses in plasma derivatives by direct contact of the amphiphiles with the plasma derivatives in solution. After treatment, the plasma proteins are separated from the amphiphiles by precipitation. Such separation may not completely remove the inactivating agents from the precipitated protein and the final product, therefore, may contain pharmaceutically harmful and/or undesirable inactivating agents.
It is, therefore, the principal object of the present invention to provide a method to substantially inactivate viruses and pyrogens in biological and pharmaceutical products.
It is another object of the present invention to completely remove the inactivating agents from the product treated to provide a pharmaceutically acceptable end product.
These and further objects as shall hereinafter appear are achieved by the present invention in a remarkable unexpected fashion as will be discerned from the following description.